The value of twin studies is well recognized at the National Institutes of Health (NIH) where an estimated 255 twin studies were funded in 2009. Twin studies have provided insights into the epidemiology, etiology, pathophysiology, and natural history of diverse disease and developmental endpoints. However, a substantial proportion of the NIH twin research portfolio supports investigations in other countries. Aside from the economic implications of this outflow of resources, questions exist about the applicability of research conducted in countries with populations unlike our own. This unfortunate situation has arisen because the U.S. lacks a national twin registry. In the U.S., there is only one state in which it is possible to establish a twin registry that is not hampered by important shortcomings. The State of Washington and the University of Washington have a grand opportunity to expand the only truly community-based twin registry in the U.S. With over 2,600 enrolled twin pairs, and more pairs joining each month, we propose to dramatically expand the University of Washington Twin Registry (UWTR) to fully realize its potential and accelerate the pace of genomic and environmental research. This effort will facilitate innovative and vital discoveries that have the potential to fundamentally change scientific thought. Our technical aims over the next 2 years are to: 1) Expand the number of participants in the Registry from 2,600 to 10,000 twin pairs;2) Build an unmatched repository that includes biological samples, including DNA collected from most pairs;3) Obtain and link informative, diverse, publicly available databases available in Washington State to phenotypic data routinely collected by the UWTR for longitudinal outcomes studies;4) Link geocoding databases that will allow unprecedented evaluation of the effects of the built environment on diverse health-related outcomes;and 5) Conduct 2 scientific integration projects that, together, demonstrate the scientific power of a large U.S. twin registry. For the 2 scientific integration projects, our scientific aims are to: 1) Conduct co-twin control and classical twin analyses of the built environment using neighborhood walkability indicators, body mass index, rates of high blood pressure, and hospitalizations;2) Perform a multi-level examination of pain perception or sensitivity, a trait linked to sleep, exercise, weight, psychological stress, and inflammatory markers such as C- reactive protein. We will use bivariate genetic modeling to determine the genetic and environmental correlations between pain sensitivity and C-reactive protein, assess the explanatory effects of specific gene polymorphisms, and explore protein-related DNA structural changes in relation to pain sensitivity. This project can transform twin research in the U.S. The creation of the UWTR as a leading twin registry and sustainable scientific resource is paramount to conducting genomic research and has unlimited potential to catalyze novel fields of research. This Registry has the potential to keep federal funding at home, conduct research more relevant to American people, and be a nexus for 21st century biomedical science. PUBLIC HEALTH RELEVANCE: Studies of twins are extraordinarily helpful for researchers trying to understand the causes and consequences of health and disease. However, the U.S. currently lacks a national registry of twins drawn from the community. In addition, most funding for twin studies comes from U.S. sources but supports international registries. This application proposes to expand the University of Washington Twin Registry to meet the needs of U.S. biomedical science.